liver biopsy in patients with chronic hcv infection . hospital de cl�nicas, university of buenos...

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416A AASLD ABSTRACTS : HEPATOLOGY October 1995 1237 TREATMENT OF HEPATOCELLULAR CARCINOMA WITH CHEMOEMBOLIZATION ANDLIVERTRANSPLANTATION. J.Fit~ueras, P.Moreno, C.Vallsi C.Benasco, J.Virgili, J.Dominguez, C.Sancho, A.Rafecas, T.Casanovas, J.Fabregat, X.Xioi, J.Torras, E.Janrrieta. C.S.U.Bellvitge.University of Barcelona. Spain. Liver transplantation (OLT) for hepatocellular carcinoma (HCCA) is controversial. Chemoembolization (TAE) is a palliative treatment for unresextable HCCA. The aim of this study isto analyze the results of TAE and OLT in the treatment of localized HCCA. 24 HCCA in cirrhotic patients were transplanted between 1991 and 1994, HCCA incidenfly discovered or the fibrolamellar variant and those arising in non cirrhotic patients were excluded of the study. TAE was carried out with 50 mg of Adriamicine, 6-16 mi of Lipiodoi and the artery was emholized with gelfoam particles, interval between TAE and OLT was 3 months. In I0 cases the diameter of the tumour was > 3cm and 6 patients had > 3 nodes, TNM status was 4T~, 9T2, 5T~ and 6T,, all cases were pNoMo. In 4 cases there was microscopic vascular invasion while 3 HCCA showed macroscopic vascular invasion. Three patients Were retransplanted due to PNF, recurrence of cirrhosis and artery thrombosis. Actuarial one year survival was 78% and 5 years 72%. OLT and TAE should be considered in the treatment of HCCA. COl 4ol col 0 ~ - 01 ) (9) (e) F2~) 12 24 36 48 80 MONTHS 1238 LIVER BIOPSY IN PATIENTS WITH CHRONIC HCV INFECTION. JA Findor. A Avaanina, JR Daruich, E Bruch laart0a, JA Sord~i. J Celeste. Hospital de Cl[nicas, U.niversity of Buenos Aires. German Hospital, Buenos Aires, Argentina. Objective~ To evaluate the frequency of histological markers of c.hron.ic HCV infection as a useful tool for diagnosis, and to study tne oegree of liver injury due to HCV. Material and methods: A consecutive serie of liver biopsy soecimens from 155 patients (pts), median age 49 years (15-73), with chronic HCV infection studied from ~anuary 1993 to Apri! 1995, wer.e analyzed by two inoepenoent observers, unw pts with 10ositivity otanti HCV (EIA 2 and RIBA 2) and HCVRNA (n- PCR), without HBV or HIV coinfection, with biopsies that showed at least three portal areas were included. Statistical analysis: The aata were grouped by 2 x 2 contingency table and analyzed by x ~ test. The continuous variables were analyzed by Kruskall Wallis test. Results: Lymphoid aggregates or follicles with or without germinal centers were found in 58 pts (37%). Ductular damage was present in 57 ~35%). Hepatocellular steatosis was oSserved in 57 (37%). une or more of these three Teatures were present in 107 (69%): The K nodell score, re.gar.d.ing the in, flammation index rangea Trom 2 to 13 and the. Tiorosis inoex from 1 to 4. Diagnosis 0T normal liver or with minimal and uncharacteristic histological changes was established in 3 pts (2%), mild chronic hepatitis in 71 (46%), moderate in 65 (42%) and severe in 16 (10%). Cirrhosis was confirmed in 23 cases (15.%)..Median age in the cirrhotic pts was 56 years (.36-68) ano in cnronic nepatitis 48 (15-73) (p = 0.0029). Conclusion: Histological features su.ch as lymphoid aggregates or follicles,. mild steatosis or ductular damage are Tre.quently present ano should be considered suggestive of the diagnosis of chronic HCV hepatitis. The nign proportion of mild chronic hepatitis with the inflammatory infiltrate confined to the portal tract is probably due to a short lasting HCV infection. The lower Trequency of the cirrhotic changes could be due to the fact that only a small proportion of pts reach the final state of liver injury or that this type of damage takes a very long time. The presence oT a smal/numoer of histologically normal liver in spite of HCVRNA +re indicates tfiat even under this circumstances the viremia is not always associated with liver injury . and that the state of chronic asymptomatic carrier is posslole. 1239 RESPONSE TO INTERFERON OF ANTI-HCV POSITIVE CHRONIC HEPATITIS PATIENTS: THE IMPACT OF QUANTITATIVE HCV-RNA RT- PCR. D Flichman. AP Colombatto, M Baldi, F Ne,qro, G Bellati 2 A Randone F Oliveri, G Colucci 3 F Bonino and MR Brunetto Dept. of GastroenteroL Molinette Hosp.Torino, 2 Div. of Med. "Crespi", Niguarda Hosp. Milano, Italy and 3 Roche Mol. Div. Basel, Switzerland. In order to study the impact of quantitative HCV-RNA RT-PCR on monitoring the response to therapy of chronic hepatitis C patients we studied the relations between the aminotransferaseSerum levels (ALT) and HCV-RNA serum levels (measured by Amplicor Monitor, Roche, Basel) in 40' anti-HCV positive (ELISA and immunoblotting) patients. Their median age was 42 y., range 21-65 y., the male female ratio was 2.3. All of them were treated with alpha interferons for at least 6 months (thrice weekly at 6 MIU) and followed-up for 6-18 months after the end of treatment. Serum specimens were obtained as follows: at least 3 samples 3-5 months before starting therapy, 2 during treatment and 2 after the end of treatment. We observed simmetric patterns of ALT and viremia in 36 cases and asymmetric in 4 cases. Twenty-nine patients (baseline viremia = 105 median, 103-106 g.Eq.ml.) with symmetric patterns showed significant but temporary (at least 1 log.) decreases of viremia. HCV-RNArebounds paralleled ALT relapses, but without quantitative relations. Five patients (baseline viremia = 103 median, 0-105 g.Eq.ml.) showed complete and persistent biochemical and virologic responses. Low levels of baseline viremia were statistically associated with response to therapy but were not predictive of recovery in single cases. Viremia and ALT patterns persisted unchanged in the remaining 4 5 2 patients (baseline viremia = 4x10 and 4 x 10 q.Eq.ml). Among 13atients with asymmetric pattern 3 (baseline viremia = 105. median, 104"105 g.Eq.ml.) showed a progressive fall and persistence of ALT levels within the normal range while their viremia fell significantly but relapsed to pretreatment levels. In the remaining patient (baseline "viremia = 104 g.Eq.ml) ALT levels did not normalize while HCV-RNA levels fell and persisted below the detection limits (1000 g.Eq.ml.). These data show a significant parallelism (in 90% of cases) between biochemical and virologic responses in interferon treated patients. Viremia levels rebounded to detectability in 96.7% of the patients with ALT relapses, however in 3 patients viremia relapsed to high levels in spite of persistently normal ALE values. The discrepancies between biochemical and virologic responses (10% of cases) might be explained by multifactodal liver diseases or coinfections with unidentified hepatotropicagents. 1240 "PSEUDOOVARIAN CARCINOMA": A /~PRESENTATION OF ADVANCED LIVER DISEASE WITH ELEVATED CA 125. ~ Flora, K Benner. Oregon Health Sciences University, Portland, OR. CA 125, a serologic tumor marker associated with more than 80% of human ovadan carcinomas has been useful both in the diagnosis of ovadan malignancy and in follow-up of treated cases. It can also be elevated in advanced liver disease. Between 1992 and 1995 we identified 9 patients with cirrhosis complicated by ascites who presented with abnormally elevated serum CA 125 levels. No patient had a history of ovarian disease. Six had undergone exploratory laparotomy because ovadan carcinQma was suspected. None of the six had ovadan lesions. Of the remaining three, two underwent liver transplantation. Intraoperatively, their ovades were normal. The third had normalization of her CA 125 with diuresis. Patient Date CA 125 Etiol. AIb P.T. Exp. # (u/ml) (gnYdl) (sec) Lap. 1 6•92 3460 ETOH 2.9 15.9 Y 2 4/95 114 ETOH 3.4 12.8 N 3 2/92 613 ETOH 2.5 13.5 Y 4 12/92 >2000 ETOH 2.4 - Y 5 5/93 367 Hep C 3.4 12,3 Y 6 11194 662 JI 2.6 13.3 Y bypass 7 1/93 >200 Hep C 2.1 - Y 8 6/93 700 ETOH 2.2 21.6 T'plant 9 5•93 191 Hep C 4.5 17.5 T'piant All patients had CA 125 levels in excess of 100 U/ml. There was no mortality associated with the laparotomies, however several patients expadenced ascitic leaks from the incision and one has had persistent massive incisional hernias.. CONCLUSION: Cirrhosis with portal hypertension should be included in the differential diagnosis of increased serum CA 125 levels and ascites. Careful preoperative ovadan imaging should be performed to minimize unnecessary surgery and patient morbidity in such patients.

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Page 1: Liver biopsy in patients with chronic HCV infection . Hospital de Cl�nicas, University of Buenos Aires. German Hospital, Buenos Aires, Argentina

416A A A S L D A B S T R A C T S : HEPATOLOGY October 1995

1237 TREATMENT OF HEPATOCELLULAR CARCINOMA WITH CHEMOEMBOLIZATION ANDLIVERTRANSPLANTATION. J.Fit~ueras, P.Moreno, C.Vallsi C.Benasco, J.Virgili, J.Dominguez, C.Sancho, A.Rafecas, T.Casanovas, J.Fabregat, X.Xioi, J.Torras, E.Janrrieta. C.S.U.Bellvitge.University of Barcelona. Spain. L iver transplantation (OLT) for hepatocellular carcinoma (HCCA) is controversial. Chemoembolization (TAE) is a palliative treatment for unresextable HCCA. The aim of this study i s t o analyze the results of TAE and OLT in the treatment of localized H C C A . 24 HCCA in cirrhotic patients were transplanted between 1991 and 1994, HCCA incidenfly discovered or the fibrolamellar variant and those arising in non cirrhotic patients were excluded of the study. TAE was carried out with 50 mg of Adriamicine, 6-16 mi o f Lipiodoi and the artery was emholized with gelfoam particles, interval between TAE and OLT was 3 months. In I0 cases the diameter o f the tumour was > 3cm and 6 patients had > 3 nodes, TNM status was 4T~, 9T2, 5T~ and 6T,, all cases were pNoMo. In 4 cases there w a s m i c r o s c o p i c vascular invasion whi le 3 H C C A s h o w e d macroscopic vascular invasion. Three patients Were retransplanted due to PNF, recurrence o f cirrhosis and artery thrombosis. Actuarial one year survival was 78% and 5 years 72%. OLT and TAE should b e c o n s i d e r e d in t h e treatment o f HCCA.

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4ol

col

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12 24 36 48 80

MONTHS

1238 LIVER BIOPSY IN PATIENTS WITH CHRONIC HCV INFECTION. JA Findor. A Avaanina, JR Daruich, E Bruch laart0a, JA Sord~i. J Celeste. Hospital de Cl[nicas, U.niversity of Buenos Aires. German Hospital, Buenos Aires, Argentina.

Objective~ To evaluate the frequency of histological markers of c.hron.ic HCV infection as a useful tool for diagnosis, and to study tne oegree of liver injury due to HCV. Material and methods: A consecutive serie o f liver biopsy soecimens from 155 patients (pts), median age 49 years (15-73), wi th chronic HCV infection studied from ~anuary 1993 to Apri! 1995, wer.e analyzed by two inoepenoent observers, u n w pts wi th 10ositivity o t a n t i HCV (EIA 2 and RIBA 2) and HCVRNA (n- PCR), w i t h o u t HBV or HIV coinfect ion, w i t h biopsies that showed at least three portal areas were included. Statistical analysis: The aata were grouped by 2 x 2 contingency table and analyzed by x ~ test. The continuous variables were analyzed by Kruskall Wallis test. Results: Lymphoid aggregates or follicles wi th or wi thout germinal centers were found in 58 pts (37%). Ductular damage was present in 57 ~35%). Hepatocellular steatosis was oSserved in 57 (37%). une or more of these three Teatures were present in 107 (69%): T h e K nodell score, re.gar.d.ing the in, f lammation index rangea Trom 2 to 13 and the. Tiorosis inoex from 1 to 4. Diagnosis 0T normal liver or wi th minimal and uncharacteristic histological changes was established in 3 pts (2%), mild chronic hepatitis in 71 (46%), moderate in 65 (42%) and severe in 16 (10%). Cirrhosis was confirmed in 23 cases (15.%)..Median age in the cirrhotic pts was 56 years (.36-68) ano in cnronic nepatitis 48 (15-73) (p = 0.0029). Conclusion: Histological features su.ch as lymphoid aggregates or follicles,. mild steatosis or ductular damage are Tre.quently present ano should be considered suggestive of the diagnosis of chronic HCV hepatitis. The nign proportion of mild chronic hepatitis wi th the inf lammatory infiltrate confined to the portal t ract is probably due to a short lasting HCV infection. The lower Trequency of the cirrhotic changes could be due to the fact that only a small proportion of pts reach the final state of liver injury or that this type of damage takes a very long time. The presence oT a smal /numoer o f histologically normal liver in spite of HCVRNA + r e indicates t f iat even under this circumstances the viremia is not always associated wi th liver injury . and that the state of chronic asymptomatic carrier is posslole.

1239 RESPONSE TO INTERFERON OF ANTI-HCV POSITIVE CHRONIC HEPATITIS PATIENTS: THE IMPACT OF QUANTITATIVE HCV-RNA RT- PCR. D Flichman. AP Colombatto, M Baldi, F Ne,qro, G Bellati 2 A Randone F Oliveri, G Colucci 3 F Bonino and MR Brunetto Dept. of GastroenteroL Molinette Hosp.Torino, 2 Div. of Med. "Crespi", Niguarda Hosp. Milano, Italy and 3 Roche Mol. Div. Basel, Switzerland.

In order to study the impact of quantitative HCV-RNA RT-PCR on monitoring the response to therapy of chronic hepatitis C patients we studied the relations between the aminotransferase Serum levels (ALT) and HCV-RNA serum levels (measured by Amplicor Monitor, Roche, Basel) in 40' anti-HCV positive (ELISA and immunoblotting) patients. Their median age was 42 y., range 21-65 y., the male female ratio was 2.3. All of them were treated with alpha interferons for at least 6 months (thrice weekly at 6 MIU) and followed-up for 6-18 months after the end of treatment. Serum specimens were obtained as follows: at least 3 samples 3-5 months before starting therapy, 2 during treatment and 2 after the end of treatment. We observed simmetric patterns of ALT and viremia in 36 cases and asymmetric in 4 cases. Twenty-nine patients (baseline viremia = 105 median, 103-106 g.Eq.ml.) with symmetric patterns showed significant but temporary (at least 1 log.) decreases of viremia. HCV-RNA rebounds paralleled ALT relapses, but without quantitative relations. Five patients (baseline viremia = 103 median, 0-105 g.Eq.ml.) showed complete and persistent biochemical and virologic responses. Low levels of baseline viremia were statistically associated with response to therapy but were not predictive of recovery in single cases. Viremia and ALT patterns persisted unchanged in the remaining

4 5 2 patients (baseline viremia = 4x10 and 4 x 10 q.Eq.ml). Among 13atients with asymmetric pattern 3 (baseline viremia = 105. median, 104"105 g.Eq.ml.) showed a progressive fall and persistence of ALT levels within the normal range while their viremia fell significantly but relapsed to pretreatment levels. In the remaining patient (baseline "viremia = 104 g.Eq.ml) ALT levels did not normalize while HCV-RNA levels fell and persisted below the detection limits (1000 g.Eq.ml.). These data show a significant parallelism (in 90% of cases) between biochemical and virologic responses in interferon treated patients. Viremia levels rebounded to detectability in 96.7% of the patients with ALT relapses, however in 3 patients viremia relapsed to high levels in spite of persistently normal ALE values. The discrepancies between biochemical and virologic responses (10% of cases) might be explained by multifactodal liver diseases or coinfections with unidentified hepatotropic agents.

1240 "PSEUDOOVARIAN CARCINOMA": A /~PRESENTATION OF ADVANCED LIVER DISEASE WITH ELEVATED CA 125. ~ Flora, K Benner. Oregon Health Sciences University, Portland, OR. CA 125, a serologic tumor marker associated with more than 80% of human ovadan carcinomas has been useful both in the diagnosis of ovadan malignancy and in follow-up of treated cases. It can also be elevated in advanced liver disease. Between 1992 and 1995 we identified 9 patients with cirrhosis complicated by ascites who presented with abnormally elevated serum CA 125 levels. No patient had a history of ovarian disease. Six had undergone exploratory laparotomy because ovadan carcinQma was suspected. None of the six had ovadan lesions. Of the remaining three, two underwent liver transplantation. Intraoperatively, their ovades were normal. The third had normalization of her CA 125 with diuresis.

Patient Date CA 125 Etiol. AIb P.T. Exp. # (u/ml) (gnYdl) (sec) Lap. 1 6•92 3460 ETOH 2.9 15.9 Y 2 4/95 114 ETOH 3.4 12.8 N 3 2/92 613 ETOH 2.5 13.5 Y 4 12/92 >2000 ETOH 2.4 - Y 5 5/93 367 He p C 3.4 12,3 Y 6 11194 662 JI 2.6 13.3 Y

bypass 7 1/93 >200 Hep C 2.1 - Y 8 6/93 700 ETOH 2.2 21.6 T'plant 9 5•93 191 Hep C 4.5 17.5 T'piant

All patients had CA 125 levels in excess of 100 U/ml. There was no mortality associated with the laparotomies, however several patients expadenced ascitic leaks from the incision and one has had persistent massive incisional hernias.. CONCLUSION: Cirrhosis with portal hypertension should be included in the differential diagnosis of increased serum CA 125 levels and ascites. Careful preoperative ovadan imaging should be performed to minimize unnecessary surgery and patient morbidity in such patients.